1. Field of the Invention
The present invention relates to a highly reactive polymer, which has a good number of carboxyl groups (or their salts) on its side chains and at the same time has a thiol group or an active group containing an activated disulfide linkage at one end of its main chain and a process for the preparation thereof. And it is an object of the present invention to provide a polymer to be used for the linking of an antitumor antibody and cytotoxic substances in the making of a target seeking anti-cancer drug (antitumor drug) which is prepared by linking said antitumor antibody, which is capable of linking with a target tumor cell, and said cytotoxic substances, which work as anti-cancer drugs.
2. Description of the Prior Art
It has hitherto been publicly known to use a reactive polymer as a medium with the object of increasing efficiency in linking an antitumor antibody and a cytotoxic substance in the preparation of a target seeking anti-cancer drug.
For instance, U.S. Pat. No. 4,046,722 (G. D. Searle & Co. Limited) issued on Sept. 6, 1977, discloses an antitumor drug which comprises an antitumor immunoglobulin and a polymer carrier, for instance, polyglutamic acid, having 5-500 molecules of a cytotoxic drug covalently bonded thereto, bonded by amide linkages. The antitumor drug obtained in this way is a very interesting chemotheraputics in that it is expected to be selectively directed to the tumor target to exert its toxic action within the tumor cell.
However, a demerit of this publicly known antitumor drug is that the linkage of this antitumor antibody and the cytotoxic part (the polymer carrier linked with an anticancer drug) is effected by amide linkages, more particularly the linkages are effected by means of free amino groups or carboxyl groups contained in the antitumor antibody. An immunoglobulin molecule has many amino groups or carboxyl groups at its antigen seeking subunit. Therefore, in an attempt to conjugate a cytotoxic substance to an antitumor immunoglobulin by means of an amide linkage, the antigen seeking subunit of the antitumor immunoglobulin also becomes conjugated with the cytotoxic substance, thus lowering its function of seeking the antigen. As a result, this poses a problem of making the obtained antitumor drug totally or partially lose its function to bind to the tumor cell. Also the method provided in U.S. Pat. No. 4,046,722 allows the formation of amide linkages in the antibody molecules and polyglutamic acid molecules, or between the same kinds of molecules. The formation of such an undesirable amide linkage results in the decreased efficacy of the obtained antitumor drug and further raises a problem to cause by-production of a high molecular weight polymer substance which is unsuited for a use for treatment of tumor patients.